Publications by authors named "Aman Prasad"

28 Publications

  • Page 1 of 1

Postoperative Radiation Therapy Refusal in Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

Laryngoscope 2021 Jul 13. Epub 2021 Jul 13.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct clinical entity with good prognosis, unique demographics, and a trend toward treatment deintensification. Patients with this disease may opt out of recommended postoperative radiation therapy (PORT) for a variety of reasons. The aim of this paper was to examine factors that predict patient refusal of recommended PORT in HPV-associated OPSCC, and the association of refusal with overall survival.

Study Design: Retrospective population-based cohort study of patients in the National Cancer Database.

Methods: We conducted a retrospective cohort study of patients in the National Cancer Database diagnosed with OPSCC between January 2010 and December 2015. We primarily assessed overall survival and the odds of refusing PORT based on demographic, socioeconomic, and clinical factors. Analysis was conducted using multivariable logistic regression and multivariable Cox proportional hazards model.

Results: A total of 4229 patients were included in the final analysis, with 156 (3.7%) patients opting out of recommended PORT. On multivariable analysis, patient refusal of PORT was independently associated with a variety of socioeconomic factors such as race, insurance status, comorbidity, treatment at a single facility, and margin status. Lastly, PORT refusal was associated with significantly lower overall survival compared to receipt of recommended PORT (hazard ratio 1.69, confidence interval 1.02-2.82).

Conclusions: Patient refusal of recommended PORT in HPV-associated OPSCC is rare and associated with variety of disease and socioeconomic factors. PORT refusal may decrease overall survival in this population. Our findings may help clinicians when counseling patients and identifying those who may be more likely to opt out of recommended adjuvant therapy.

Level Of Evidence: 3 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29743DOI Listing
July 2021

Impact of Race and Insurance Status on Primary Treatment for HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2021 Jul 13:1945998211029839. Epub 2021 Jul 13.

Department of Otolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: To assess the impact of sociodemographic factors on primary treatment choice (surgery vs radiotherapy) in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC).

Study Design: Retrospective analysis of the National Cancer Database.

Setting: Data from >1500 Commission on Cancer institutions (academic and community) via the National Cancer Database.

Methods: Our sample consists of patients diagnosed with HPV+ OPSCC from 2010 to 2015. The primary outcome of interest was initial treatment modality: surgery vs radiation. We performed multivariable logistic models to assess the relationship between treatment choice and sociodemographic factors, including sex, race, treatment facility, and insurance status.

Results: Of the 16,043 patients identified, 5894 (36.7%) underwent primary surgery while 10,149 (63.3%) received primary radiotherapy. Black patients were less likely than White patients to receive primary surgery (odds ratio [OR], 0.80; 95% CI, 0.66-0.96). When compared with privately insured patients, those who were uninsured or on Medicaid or Medicare were also less likely to receive primary surgery (OR, 0.70 [95% CI, 0.56-0.86]; OR, 0.77 [95% CI, 0.65-0.91]; OR, 0.85 [95% CI, 0.75-0.96], respectively). Patients receiving treatment at an academic/research cancer program were more likely to undergo primary surgery than those treated at comprehensive community cancer programs (OR, 1.33; 95% CI, 1.14-1.56).

Conclusion: In this large sample of patients with HPV+ OPSCC, race and insurance status affect primary treatment choice. Specifically, Black and nonprivately insured patients are less likely to receive primary surgery as compared with White or privately insured patients. Our findings illuminate potential disparities in HPV+ OPSCC treatment.
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http://dx.doi.org/10.1177/01945998211029839DOI Listing
July 2021

Palliative care in metastatic head and neck cancer.

Head Neck 2021 09 21;43(9):2764-2777. Epub 2021 May 21.

Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Background: Due to inherent impact on quality of life, metastatic head and neck cancer patients are well-suited to benefit from palliative care (PC). Our objective was to examine factors that shape PC utilization and implications for overall survival in stage IVc head and neck cancer patients.

Methods: A retrospective study of patients with stage IVc head and neck cancer in the National Cancer Database from 2004 and 2015 was conducted.

Results: 7794 cases met inclusion criteria, of which 19.3% received PC. PC use was associated with more recent years of diagnosis, Northeast facility geography, and non-private insurances (p < 0.05). Compared to no PC, "interventional" PC, defined as palliative surgery, radiation, and/or chemotherapy, and "pain management only" PC were associated with lower overall survival (p < 0.05).

Conclusions: PC use increased over time and was associated with demographic and clinical factors. There remains opportunity for improvement in optimal implementation of palliative care.
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http://dx.doi.org/10.1002/hed.26761DOI Listing
September 2021

Critical review of clinical practice guidelines for evaluation of neck mass in adults.

Braz J Otorhinolaryngol 2021 Apr 10. Epub 2021 Apr 10.

University of Pennsylvania, Department of Otorhinolaryngology, Philadelphia, PA, USA; University of Pennsylvania, Leonard Davis Institute of Health Economics, Philadelphia, PA, USA. Electronic address:

Objective: Several clinical practice guidelines have been produced and disseminated for the evaluation of a neck mass. However, to date, the quality and methodologic rigor of these clinical practice guidelines have not been appraised. Therefore, this study set out to identify and assess the methodologic quality of national and international guidelines for the evaluation and management of neck masses in adults.

Methods: We conducted a comprehensive search of EMBASE, MEDLINE/PubMed, SCOPUS and grey literature sources until September 2020. The quality of these guidelines was assessed by four reviewers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II). Domain scores were considered acceptable quality if they scored >60%, and Intraclass Correlation Coefficients (ICC) were calculated to assess agreement among the appraisers.

Results: Seven guidelines were assessed for evaluation. Among these, only the American Academy of Otolaryngology (AAO), Cancer Care Manitoba (CCMB), and the American Society of Clinical Oncology (ASCO) achieved an overall rating of "high". The remaining four guidelines achieved ratings of either "average" or "low". The "Scope and Purpose" domain achieved the highest mean score (94.4%±5.0%), and lowest was "Applicability" (51.5%±29.2%). ICC analysis showed substantial to very good agreement across all domains (0.75-0.98).

Conclusion: These findings highlight the variability in methodologic quality of guidelines for the evaluation and management of adult neck mass. The results from this analysis highlight the need to improve guidelines development process for this topic and may guide the selection and use of these guidelines in clinical practice.
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http://dx.doi.org/10.1016/j.bjorl.2021.03.005DOI Listing
April 2021

Telehealth Utilization in Response to the COVID-19 Pandemic in Pediatric Orthopaedic Surgery.

J Am Acad Orthop Surg 2021 Apr 16. Epub 2021 Apr 16.

From the Harvard Medical School & Boston Children's Hospital, Boston, MA (Parisien), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (Shin and Prasad), Columbia University Medical Center, New York City, NY (Trofa and Levine), Boston University Medical Center (Li), Boston, MA, and The Children's Hospital of Philadelphia, Philadelphia, PA (Parisien, Flynn, and Ganley).

Introduction: The purpose of this investigation was to assess the utilization of telehealth capabilities by pediatric orthopaedic departments across the United States in response to the COVID-19 pandemic.

Methods: One hundred four pediatric orthopaedic departments were investigated regarding each institution's current telehealth utilization as a direct response to the COVID-19 pandemic.

Results: Of the 104 hospitals contacted across the United States, 100 pediatric orthopaedic departments in 39 states responded for an overall response rate of 96%. Of the 95 institutions offering telehealth services, 83 (87.4%) cited the COVID-19 pandemic as the impetus for the implementation of telehealth services. Of these, 29 institutions (31%) began offering services from March 16 to March 31 and 34 (36%) began offering services from April 1 to April 15. Regional analysis demonstrated an 800% increase in telehealth services in the state of New York, a 600% increase in Florida, a 500% increase in Texas, a 400% increase in Michigan, a 200% increase in Pennsylvania, and a 1,100% increase in California.

Discussion: This study demonstrates the rapid response measures instituted by pediatric orthopaedic institutions to meet the fundamental needs of the pediatric population during this unprecedented pandemic.
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http://dx.doi.org/10.5435/JAAOS-D-20-00694DOI Listing
April 2021

Appraisal of clinical practice guidelines for the evaluation and management of neck masses in children.

J Paediatr Child Health 2021 06 20;57(6):803-809. Epub 2021 Apr 20.

Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

Aim: The purpose of this systematic review was to use the Appraisal of Guidelines for Research and Evaluation tool to assess the methodological quality of clinical practice guidelines (CPGs) for the workup and management of paediatric neck masses.

Methods: MEDLINE, Embase, Cochrane and grey literature were searched to identify CPG incorporating paediatric neck masses. Four authors with previous training of the Appraisal of Guidelines for Research and Evaluation tool evaluated the included studies.

Results: Nine studies met inclusion criteria. The highest scoring domains were 'Scope and Purpose' (74.0 ± 4.5) and 'Clarity of Presentation' (72.9 ± 6.3). The lowest scoring domains were 'Rigour and Development' (18.8 ± 7.5) and 'Applicability' (23.7 ± 6.1). One study was 'High' quality, three received scores of 'Average' and five were found to be 'Low' quality.

Conclusion: The majority of paediatric neck mass CPGs were low to average quality. The domains in need of greatest improvement were 'Rigour and Development' and 'Applicability', suggesting significant concerns in current CPGs focused on paediatric neck masses.
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http://dx.doi.org/10.1111/jpc.15516DOI Listing
June 2021

Primary Orbital Melanoma: An Investigation of a Rare Malignancy Using the National Cancer Database.

Laryngoscope 2021 08 11;131(8):1790-1797. Epub 2021 Feb 11.

Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objectives: Primary orbital melanoma (POM) is a rare disease with limited data on survival and best treatment practices. Here we utilize the National Cancer Database (NCDB) to determine the overall survival (OS) and covariates that influence mortality.

Study Design: Retrospective cohort study.

Methods: All patients diagnosed with POM from 2004 to 2016 were identified in the NCDB. Patient and oncologic data were analyzed using the Kaplan-Meier method and multivariate models for the primary outcome of OS.

Results: A total of 129 patients were identified. Median OS was 36.9 months (95% confidence interval [CI] 24.1-78.7 months) with mean 5-year survival of 42.0% (CI 33.2%-53.2%). Treatments received included surgery alone (43.4%), radiation alone (23.3%), and surgery followed by radiation (20.2%). The multivariate model demonstrated an increased risk of death associated with age over 80 years (hazard ratio [HR] 3.41, CI 1.31-8.86, P = .012), a Charlson-Deyo comorbidity score of 2 or greater (HR 5.30, CI 1.87-15.03, P = .002), and no treatment (HR 2.28, CI 1.03-5.06, P = .042). For every 1 cm increase in tumor size, there was an increased risk of death (HR 1.06, CI 1.00-1.13, P = .039). When compared to surgery alone, no other treatment modality had an effect on OS.

Conclusions: This study leveraged multiyear data from the NCDB to provide prognostic and demographic information on the largest known cohort of POM cases. Increased age, increased comorbidities, not receiving treatment, and larger tumor size were associated with increased mortality. There was no clear survival advantage for specific treatments.

Level Of Evidence: 4 Laryngoscope, 131:1790-1797, 2021.
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http://dx.doi.org/10.1002/lary.29428DOI Listing
August 2021

Resident Safety Huddles: Our Department's Experience in Improving Safety Culture.

Laryngoscope 2021 06 13;131(6):E1811-E1815. Epub 2021 Jan 13.

Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, U.S.A.

Objective/hypothesis: Our department sought to develop a quality improvement initiative in the interest of promoting resident involvement within the departmental safety culture. Specifically, we aimed to identify any barriers to incident reporting among residents and to create an approach to rectify this problem.

Study Design: Patient Safety/Quality Improvement.

Methods: This is a descriptive, qualitative study taking place at a large teaching hospital. A brief survey was administered to all Otorhinolaryngology residents and based on feedback a two-pronged approach to creating a patient safety and quality improvement curriculum was undertaken. This entailed implementation of 1) a formalized online curriculum and 2) a resident-driven forum for discussion of safety concerns termed a "Resident Safety Huddle."

Results: The survey identified three main barriers to incident reporting among residents, including increased workload, the punitive nature of the system, and fear of retribution. During the study period, the residents completed the curriculum required to obtain the Institute for Healthcare Improvement Basic Certificate of Quality and Safety and participated in 10 Resident Safety Huddles. Each huddle was dedicated to discussion of a unique safety concern and frequently led to sustainable solutions. After implementation of this curriculum, an increase in the number of safety events reported by residents was recognized.

Conclusions: In building an educational foundation for incident reporting and further bolstering it with a resident-driven forum for discussion of safety concerns, we were able to achieve a recognizable and meaningful impact on our residents and the greater departmental safety culture.

Level Of Evidence: 4 (single descriptive or qualitative study) Laryngoscope, 131:E1811-E1815, 2021.
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http://dx.doi.org/10.1002/lary.29384DOI Listing
June 2021

Role of elective neck dissection and adjuvant radiation therapy in patients with polymorphous adenocarcinoma.

Eur Arch Otorhinolaryngol 2021 Sep 3;278(9):3459-3466. Epub 2021 Jan 3.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, 800 Walnut Street, 18th Floor, Philadelphia, PA, 19107, USA.

Purpose: To evaluate the role of elective neck dissection (END) and of adjuvant radiation (aRT) in polymorphous adenocarcinoma (PAC), previously known as polymorphous low-grade adenocarcinoma (PLGA).

Methods: Retrospective cohort study of patients in the National Cancer Database with a histology of PAC (coded as PLGA) at a head and neck site diagnosed between 2004 and 2015. Multivariable Cox proportional hazard modeling was used to assess overall survival in the overall population, and in sub-analyses of clinically N0 disease, positive resection margins, and late stage disease.

Results: A total of 922 patients [66.8% female; mean (SD) age, 60.9 (13.9) years] met inclusion criteria. 74.7% of patients received surgery alone, and 18.0% received surgery and aRT. Only 7.6% of patients with clinically N0 disease received an END, with 10.6% of these having at least one positive node. END did not have a survival benefit compared to no END [HR 1.28 (0.61-2.68)]. Compared to surgery alone, aRT did not have significantly increased survival in the overall population or in late stage [HR 0.68 (0.39-1.19) and HR 0.46 (0.18-1.22), respectively]. On sub-analysis of patients with positive resection margins, aRT had a significant survival benefit compared to surgery alone [HR 0.37 (0.14-0.99)].

Conclusion: PAC is a rare, slow-growing malignant tumor typically treated with surgical excision, with undefined indications for END or aRT. Our findings show END to not have a benefit to overall survival. In patients with positive resection margins, there was a survival benefit for aRT.
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http://dx.doi.org/10.1007/s00405-020-06539-xDOI Listing
September 2021

Propensity score matching in otolaryngologic literature: A systematic review and critical appraisal.

PLoS One 2020 31;15(12):e0244423. Epub 2020 Dec 31.

Biostatistics Analysis Center, University of Pennsylvania, Philadelphia, PA, United States of America.

Background: Propensity score techniques can reduce confounding and bias in observational studies. Such analyses are able to measure and balance pre-determined covariates between treated and untreated groups, leading to results that can approximate those generated by randomized prospective studies when such trials are not feasible. The most commonly used propensity score -based analytic technique is propensity score matching (PSM). Although PSM popularity has continued to increase in medical literature, improper methodology or methodological reporting may lead to biased interpretation of treatment effects or limited scientific reproducibility and generalizability. In this study, we aim to characterize and assess the quality of PSM methodology reporting in high-impact otolaryngologic literature.

Methods: PubMed and Embase based systematic review of the top 20 journals in otolaryngology, as measured by impact factor from the Journal Citations Reports from 2012 to 2018, for articles using PSM analysis throughout their publication history. Eligible articles were reviewed and assessed for quality and reporting of PSM methodology.

Results: Our search yielded 101 studies, of which 92 were eligible for final analysis and review. The proportion of studies utilizing PSM increased significantly over time (p < 0.001). Nearly all studies (96.7%, n = 89) specified the covariates used to calculate propensity scores. Covariate balance was illustrated in 67.4% (n = 62) of studies, most frequently through p-values. A minority (17.4%, n = 16) of studies were found to be fully reproducible according to previously established criteria.

Conclusions: While PSM analysis is becoming increasingly prevalent in otolaryngologic literature, the quality of PSM methodology reporting can be improved. We provide potential recommendations for authors regarding optimal reporting for analyses using PSM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244423PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774981PMC
March 2021

Preparing for Telemedicine Visits: Guidelines and Setup.

Front Med (Lausanne) 2020 25;7:600794. Epub 2020 Nov 25.

Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

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http://dx.doi.org/10.3389/fmed.2020.600794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724018PMC
November 2020

Allergic contact dermatitis to silicone in a continuous positive airway pressure mask.

Contact Dermatitis 2021 Jun 27;84(6):460-462. Epub 2020 Dec 27.

Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

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http://dx.doi.org/10.1111/cod.13759DOI Listing
June 2021

Snapshot Impact of COVID-19 on Mental Wellness in Nonphysician Otolaryngology Health Care Workers: A National Study.

OTO Open 2020 Jul-Sep;4(3):2473974X20948835. Epub 2020 Aug 7.

Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: Nonphysician health care workers are involved in high-risk patient care during the COVID-19 pandemic, placing them at high risk of mental health burden. The mental health impact of COVID-19 in this crucial population has not been studied thus far. Thus, the objective of this study is to assess the psychosocial well-being of these providers.

Study Design: National cross-sectional online survey (no control group).

Setting: Academic otolaryngology programs in the United States.

Subjects And Methods: We distributed a survey to nonphysician health care workers in otolaryngology departments across the United States. The survey incorporated a variety of validated mental health assessment tools to measure participant burnout (Mini-Z assessment), anxiety (Generalized Anxiety Disorder-7), distress (Impact of Event Scale), and depression (Patient Health Questionnaire-2). Multivariable logistic regression analysis was performed to determine predictive factors associated with these mental health outcomes.

Results: We received 347 survey responses: 248 (71.5%) nurses, 63 (18.2%) administrative staff, and 36 (10.4%) advanced practice providers. A total of 104 (30.0%) respondents reported symptoms of burnout; 241 (69.5%), symptoms of anxiety; 292 (84.1%), symptoms of at least mild distress; and 79 (22.8%), symptoms of depression. Upon further analysis, development of these symptoms was associated with factors such as occupation, practice setting, and case load.

Conclusion: Frontline otolaryngology health care providers exhibit high rates of mental health complications, particularly anxiety and distress, in the wake of COVID-19. Adequate support systems must be put into place to address these issues.
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http://dx.doi.org/10.1177/2473974X20948835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415941PMC
August 2020

Patient Perceptions of Head and Neck Ambulatory Telemedicine Visits: A Qualitative Study.

Otolaryngol Head Neck Surg 2021 05 14;164(5):923-931. Epub 2020 Jul 14.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: During the COVID-19 pandemic, there has been unprecedented use of telemedicine for otolaryngology ambulatory visits. Patient satisfaction with telemedicine is an important metric, but survey-based questionnaires do not capture the nuances of the patient experience. This study aims to understand head and neck patients' perceptions about telemedicine clinic visits during COVID-19.

Methods: Fifty-six established patients who had video-based telemedicine visits with an otolaryngology-head and neck surgery faculty member between March 25, 2020, and April 24, 2020, completed unstructured telephone interviews. Conventional content analysis was used to analyze the interview data. Retrospective chart reviews were conducted to determine the patients' demographic, disease, and treatment information.

Results: The primary benefits of telemedicine were accessibility and cost and time savings. Primary limitations included the ability to perform a physical examination. Most patients expressed a willingness to participate in future remote visits if appropriate or necessitated by social circumstances.

Discussion: Telemedicine is a disruptive process, and long-term adoption requires understanding patient perception of and satisfaction with telemedicine. Head and neck cancer patients were generally satisfied with telemedicine. The study elucidated patient perceived benefits and limitations of telemedicine.

Implications For Practice: Continued implementation of telemedicine in otolaryngology-head and neck ambulatory clinics will require consideration of contextual features surrounding the virtual delivery of care, with particular attention to visit appropriateness for telemedicine and social circumstances.
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http://dx.doi.org/10.1177/0194599820943523DOI Listing
May 2021

Mental health among otolaryngology resident and attending physicians during the COVID-19 pandemic: National study.

Head Neck 2020 Jul 4;42(7):1597-1609. Epub 2020 Jun 4.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Otolaryngologists are among the highest risk for COVID-19 exposure.

Methods: This is a cross-sectional, survey-based, national study evaluating academic otolaryngologists. Burnout, anxiety, distress, and depression were assessed by the single-item Mini-Z Burnout Assessment, 7-item Generalized Anxiety Disorder Scale, 15-item Impact of Event Scale, and 2-item Patient Health Questionnaire, respectively.

Results: A total of 349 physicians completed the survey. Of them, 165 (47.3%) were residents and 212 (60.7%) were males. Anxiety, distress, burnout, and depression were reported in 167 (47.9%), 210 (60.2%), 76 (21.8%), and 37 (10.6%) physicians, respectively. Attendings had decreased burnout relative to residents (odds ratio [OR] 0.28, confidence interval [CI] [0.11-0.68]; P = .005). Females had increased burnout (OR 1.93, CI [1.12.-3.32]; P = .018), anxiety (OR 2.53, CI [1.59-4.02]; P < .005), and distress (OR 2.68, CI [1.64-4.37]; P < .005). Physicians in states with greater than 20 000 positive cases had increased distress (OR 2.01, CI [1.22-3.31]; P = .006).

Conclusion: During the COVID-19 pandemic, the prevalence of burnout, anxiety, and distress is high among academic otolaryngologists.
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http://dx.doi.org/10.1002/hed.26292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300862PMC
July 2020

Telemedicine for head and neck ambulatory visits during COVID-19: Evaluating usability and patient satisfaction.

Head Neck 2020 Jul 1;42(7):1681-1689. Epub 2020 Jun 1.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: In light of the COVID-19 pandemic, there has been a rapid increase in telemedicine visits. Otolaryngology patient satisfaction with these visits has not yet been extensively studied using a validated survey.

Methods: All patients who had telemedicine visits with three head and neck surgeons, by phone or video-based platform, between March 25, 2020 and April 24, 2020. Retrospective chart reviews were conducted to determine demographic, disease, and treatment information. Patients who had a video visit were contacted by telephone and, if they could be reached and consented, were administered the telehealth usability questionnaire (TUQ).

Results: Hundred surveys were completed. The average score across all questions was 6.01 on a scale from 1 to 7, where 7 indicated the highest level of patient agreement. The highest scores were for questions related to satisfaction with telehealth (6.29), while the lowest were related to reliability (4.86).

Conclusions: Patients are generally highly satisfied with telemedicine.
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http://dx.doi.org/10.1002/hed.26285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300847PMC
July 2020

Optimizing your telemedicine visit during the COVID-19 pandemic: Practice guidelines for patients with head and neck cancer.

Head Neck 2020 06 28;42(6):1317-1321. Epub 2020 Apr 28.

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

The COVID-19 epidemic has resulted in many hospitals and practices to cancel in-person outpatient clinic visits, where head and neck patients receive their critical longitudinal care. Out of necessity, most practices have been encouraged to use telemedicine as a method to maintain a continuum of care with their patients. As a result, the prevalence of telemedicine has grown rapidly during this pandemic, without allowing the physicians and patients to be adequately educated on how best to utilize the services. There is a steep learning curve as we have learned, and our goal is to provide guidelines for both patients and physicians, as well as a valuable patient handout in preparation for their visit.
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http://dx.doi.org/10.1002/hed.26197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267295PMC
June 2020

Head and neck virtual medicine in a pandemic era: Lessons from COVID-19.

Head Neck 2020 06 22;42(6):1308-1309. Epub 2020 Apr 22.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

The 2019 novel coronavirus disease (COVID-19) has presented the world and physicians with a unique public health challenge. In light of its high transmissibility and large burden on the health care system, many hospitals and practices have opted to cancel elective surgeries in order to mobilize resources, ration personal protective equipment and guard patients from the virus. Head and neck cancer physicians are particularly affected by these changes given their scope of practice, complex patient population, and interventional focus. In this viewpoint, we discuss some of the many challenges faced by head and neck surgeons in this climate. Additionally, we outline the utility of telemedicine as a potential strategy for allowing physicians to maintain an effective continuum of care.
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http://dx.doi.org/10.1002/hed.26174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262175PMC
June 2020

Metabolic Rewiring in Response to Biguanides Is Mediated by mROS/HIF-1a in Malignant Lymphocytes.

Cell Rep 2019 12;29(10):3009-3018.e4

Department of Dermatology, University of Wisconsin-Madison, Madison, WI 53706, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA. Electronic address:

Metabolic flexibility allows cells to adapt to various environments and limits the efficacy of metabolic drugs. Therapeutic targeting of cancer metabolism relies on defining limiting requirements and vulnerabilities in the highly dynamic metabolic network. Here, we characterize the metabolic reprogramming and identify cancer-specific metabolic vulnerabilities in response to the pharmacological inhibition of mitochondrial complex I. Our work reveals the adaptation mechanism in malignant lymphocytes providing resistance against the biguanides phenformin and metformin by transcriptionally reprogramming glucose metabolism. Metabolic adaptation to complex I inhibition is mediated by mitochondrial reactive oxygen species (mROS) serving as a mitochondrial stress signal activating hypoxia-inducible factor-1a (HIF-1a). Inhibition of the mROS/HIF-1a axis through antioxidants or direct suppression of HIF-1a selectively disrupts metabolic adaptation and survival during complex I dysfunction in malignant lymphocytes. Our results identify HIF-1a signaling as a critical factor in resistance against biguanide-induced mitochondrial dysfunction, allowing selective targeting of metabolic pathways in leukemia and lymphoma.
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http://dx.doi.org/10.1016/j.celrep.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385748PMC
December 2019

Toward Identifying Subnetworks from FBF Binding Landscapes in Spermatogenic or Oogenic Germlines.

G3 (Bethesda) 2019 01 9;9(1):153-165. Epub 2019 Jan 9.

Department of Biochemistry, University of Wisconsin-Madison, Wisconsin 53706

Metazoan PUF (Pumilio and FBF) RNA-binding proteins regulate various biological processes, but a common theme across phylogeny is stem cell regulation. In , FBF ( Binding Factor) maintains germline stem cells regardless of which gamete is made, but FBF also functions in the process of spermatogenesis. We have begun to "disentangle" these biological roles by asking which FBF targets are gamete-independent, as expected for stem cells, and which are gamete-specific. Specifically, we compared FBF iCLIP binding profiles in adults making sperm to those making oocytes. Normally, XX adults make oocytes. To generate XX adults making sperm, we used a mutant requiring growth at 25°; for comparison, wild-type oogenic hermaphrodites were also raised at 25°. Our FBF iCLIP data revealed FBF binding sites in 1522 RNAs from oogenic adults and 1704 RNAs from spermatogenic adults. More than half of these FBF targets were independent of germline gender. We next clustered RNAs by FBF-RNA complex frequencies and found four distinct blocks. Block I RNAs were enriched in spermatogenic germlines, and included validated target , while Block II and III RNAs were common to both genders, and Block IV RNAs were enriched in oogenic germlines. Block II (510 RNAs) included almost all validated FBF targets and was enriched for cell cycle regulators. Block III (21 RNAs) was enriched for RNA-binding proteins, including previously validated FBF targets and We suggest that Block I RNAs belong to the FBF network for spermatogenesis, and that Blocks II and III are associated with stem cell functions.
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http://dx.doi.org/10.1534/g3.118.200300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325917PMC
January 2019

An RNA-Binding Multimer Specifies Nematode Sperm Fate.

Cell Rep 2018 06;23(13):3769-3775

Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:

FOG-3 is a master regulator of sperm fate in Caenorhabditis elegans and homologous to Tob/BTG proteins, which in mammals are monomeric adaptors that recruit enzymes to RNA binding proteins. Here, we determine the FOG-3 crystal structure and in vitro demonstrate that FOG-3 forms dimers that can multimerize. The FOG-3 multimeric structure has a basic surface potential, suggestive of binding nucleic acid. Consistent with that prediction, FOG-3 binds directly to nearly 1,000 RNAs in nematode spermatogenic germ cells. Most binding is to the 3' UTR, and most targets (94%) are oogenic mRNAs, even though assayed in spermatogenic cells. When tethered to a reporter mRNA, FOG-3 represses its expression. Together these findings elucidate the molecular mechanism of sperm fate specification and reveal the evolution of a protein from monomeric to multimeric form with acquisition of a distinct mode of mRNA repression.
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http://dx.doi.org/10.1016/j.celrep.2018.05.095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066285PMC
June 2018

A CS1-NKG2D Bispecific Antibody Collectively Activates Cytolytic Immune Cells against Multiple Myeloma.

Cancer Immunol Res 2018 07 16;6(7):776-787. Epub 2018 May 16.

Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.

Multiple myeloma (MM) is an incurable hematologic malignancy of plasma cells, with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single-chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb). Although NKG2D is a potent activation receptor ubiquitously expressed on mostly cytolytic immune cells including NK cells, CD8 T cells, γδ T cells, and NKT cells, the CS1 tumor-associated antigen on MM represents a promising target. CS1-NKG2D biAb engaged human MM cell lines and NKG2D immune cells, forming immune synapses. In effector cells, CS1-NKG2D biAb triggered the phosphorylation of AKT, a downstream protein kinase of the activated NKG2D-DAP10 complex. The EC values of CS1-NKG2D biAb for CS1 and for CS1 MM cell lines with effector PBMCs were 10 and 10 mol/L, respectively. CS1-NKG2D biAb acted through multiple types of immune cells, and this induced cytotoxicity was both CS1- and NKG2D-specific. , survival was significantly prolonged using CS1-NKG2D biAb in a xenograft NOD-SCID (NSG) mouse model engrafted with both human PBMCs and MM cell lines. Collectively, we demonstrated that the CS1-NKG2D biAb facilitated an enhanced immune synapse between CS1 MM cells and NKG2D cytolytic innate and antigen-specific effector cells, which, in turn, activated these immune cells for improved clearance of MM. .
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http://dx.doi.org/10.1158/2326-6066.CIR-17-0649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030494PMC
July 2018

Survey Assessing Medical Student and Physician Knowledge and Attitudes Regarding the Opioid Crisis.

WMJ 2018 Mar;117(1):34-37

University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Background: There is a national opioid misuse and overdose crisis. Consensus guidelines seek to inform practice and reduce risk; however, effect on clinician attitudes and knowledge remains unclear.

Methods: We surveyed 228 medical students and physicians in Wisconsin to assess their knowledge regarding at-risk patients, alternatives to opioids, and best treatment practices for opioid addiction. We also assessed attitudes about prescribing naloxone, relapse likelihood, and responsibility for the crisis.

Discussion: Enhancement of opioid-related education is both necessary to address knowledge gaps and desired by students and physicians.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098698PMC
March 2018

The PUF binding landscape in metazoan germ cells.

RNA 2016 07 10;22(7):1026-43. Epub 2016 May 10.

Department of Biochemistry, and Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

PUF (Pumilio/FBF) proteins are RNA-binding proteins and conserved stem cell regulators. The Caenorhabditis elegans PUF proteins FBF-1 and FBF-2 (collectively FBF) regulate mRNAs in germ cells. Without FBF, adult germlines lose all stem cells. A major gap in our understanding of PUF proteins, including FBF, is a global view of their binding sites in their native context (i.e., their "binding landscape"). To understand the interactions underlying FBF function, we used iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation) to determine binding landscapes of C. elegans FBF-1 and FBF-2 in the germline tissue of intact animals. Multiple iCLIP peak-calling methods were compared to maximize identification of both established FBF binding sites and positive control target mRNAs in our iCLIP data. We discovered that FBF-1 and FBF-2 bind to RNAs through canonical as well as alternate motifs. We also analyzed crosslinking-induced mutations to map binding sites precisely and to identify key nucleotides that may be critical for FBF-RNA interactions. FBF-1 and FBF-2 can bind sites in the 5'UTR, coding region, or 3'UTR, but have a strong bias for the 3' end of transcripts. FBF-1 and FBF-2 have strongly overlapping target profiles, including mRNAs and noncoding RNAs. From a statistically robust list of 1404 common FBF targets, 847 were previously unknown, 154 were related to cell cycle regulation, three were lincRNAs, and 335 were shared with the human PUF protein PUM2.
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http://dx.doi.org/10.1261/rna.055871.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911911PMC
July 2016

NeuCode Labeling in Nematodes: Proteomic and Phosphoproteomic Impact of Ascaroside Treatment in Caenorhabditis elegans.

Mol Cell Proteomics 2015 Nov 21;14(11):2922-35. Epub 2015 Sep 21.

From the Departments of ‡Chemistry, §Biomolecular Chemistry, ¶Genome Center,

The nematode Caenorhabditis elegans is an important model organism for biomedical research. We previously described NeuCode stable isotope labeling by amino acids in cell culture (SILAC), a method for accurate proteome quantification with potential for multiplexing beyond the limits of traditional stable isotope labeling by amino acids in cell culture. Here we apply NeuCode SILAC to profile the proteomic and phosphoproteomic response of C. elegans to two potent members of the ascaroside family of nematode pheromones. By consuming labeled E. coli as part of their diet, C. elegans nematodes quickly and easily incorporate the NeuCode heavy lysine isotopologues by the young adult stage. Using this approach, we report, at high confidence, one of the largest proteomic and phosphoproteomic data sets to date in C. elegans: 6596 proteins at a false discovery rate ≤ 1% and 6620 phosphorylation isoforms with localization probability ≥75%. Our data reveal a post-translational signature of pheromone sensing that includes many conserved proteins implicated in longevity and response to stress.
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http://dx.doi.org/10.1074/mcp.M115.049684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638036PMC
November 2015

Amorfrutins are potent antidiabetic dietary natural products.

Proc Natl Acad Sci U S A 2012 May 16;109(19):7257-62. Epub 2012 Apr 16.

Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.
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http://dx.doi.org/10.1073/pnas.1116971109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358853PMC
May 2012

Tool for estimating the risk of anthropogenic spread of Batrachochytrium denrobatidis between water bodies.

Ecohealth 2009 Mar 7;6(1):16-9. Epub 2009 May 7.

Department of Biological Sciences, Idaho State University, Pocatello, ID 83209, USA.

Batrachochytrium dendrobatidis (Bd) is a chytrid fungus, which has been associated with numerous amphibian mortality events around the world. It is hypothesized that Bd was inadvertently spread through human activities. We have developed a basic risk assessment tool to better understand the potential risk of transferring Bd between water bodies through field activities, and to target disinfection strategies which reduce the risk of spreading Bd. The questions in the risk assessment focus on the likelihood of Bd being present at sites, the likelihood of transferring the pathogen from one site to another, and the impact of transferring the pathogen. Identified risk factors include the presence of amphibians in the visited areas, the presence of Bd in one or more of the sites and in the surrounding area, the number of visitors to the sites, direct contact with amphibians, and the sharing of equipment between sites. The risk assessment tool can be found on the Internet at: (http://www.cefas.co.uk/4449.aspx).
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http://dx.doi.org/10.1007/s10393-009-0227-zDOI Listing
March 2009
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